(S)-N-Benzyl-2-methyl-1,2,3,4-tetra­hydro­isoquinoline-3-carboxamide

Tricia Naicker; Thavendran Govender; Hendrik G Kruger; Glenn EM Maguire

doi:10.1107/S1600536810050361

. 2010 Dec 11;67(Pt 1):o67. doi: 10.1107/S1600536810050361

(S)-N-Benzyl-2-methyl-1,2,3,4-tetrahydroisoquinoline-3-carboxamide

Tricia Naicker ^a, Thavendran Govender ^a, Hendrik G Kruger ^b, Glenn EM Maguire ^b,^*

PMCID: PMC3050362 PMID: 21522778

Abstract

The structure of the title compound, C₁₈H₂₀N₂O, at 173 K has hexagonal (P6₁) symmetry. The N-containing six-membered ring assumes a half-chair conformation. In the crystal, intermolecular N—H⋯O hydrogen bonding via the amide groups cross-link the molecules along the a axis. The absolute configuration was confirmed by 2D NMR studies.

Related literature

The title compound is a precursor to chiral ligands involving a tetrahydroisoquinoline backbone. For the application of these ligands as catalysts, see: Chakka et al. (2009 ▶); Peters et al. (2010 ▶); Naicker et al. (2010a ▶). For related structures, see: Chakka et al. (2010 ▶). For a related structure with the same chiral centre and conformation of the six-membered ring, see: Naicker et al. (2010b ▶).

Experimental

Crystal data

C₁₈H₂₀N₂O
M _r = 280.36
Hexagonal,
a = 10.1838 (13) Å
c = 25.965 (3) Å
V = 2332.1 (5) Å³
Z = 6
Mo Kα radiation
μ = 0.08 mm⁻¹
T = 173 K
0.22 × 0.12 × 0.03 mm

Data collection

Bruker Kappa DUO APEXII diffractometer
18777 measured reflections
1759 independent reflections
1358 reflections with I > 2σ(I)
R _int = 0.059

Refinement

R[F ² > 2σ(F ²)] = 0.036
wR(F ²) = 0.088
S = 1.05
1759 reflections
195 parameters
2 restraints
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.14 e Å⁻³
Δρ_min = −0.14 e Å⁻³

Data collection: APEX2 (Bruker, 2006 ▶); cell refinement: SAINT (Bruker, 2006 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: OLEX2 (Dolomanov et al., 2009 ▶); software used to prepare material for publication: SHELXL97.

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536810050361/hg2752sup1.cif

e-67-00o67-sup1.cif^{(19.1KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536810050361/hg2752Isup2.hkl

e-67-00o67-Isup2.hkl^{(86.7KB, hkl)}

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N2—H2⋯O1ⁱ	0.96 (2)	1.92 (2)	2.852 (3)	165 (3)

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Symmetry code: (i) Inline graphic .

Acknowledgments

The authors wish to thank Dr Hong Su of the Chemistry Department of the University of Cape Town for her assistance with the crystallographic data collection.

supplementary crystallographic information

Comment

The title compound (Fig. 1) is a precursor in the synthesis of novel chiral ligands involving a tetrahydroisoquinoline backbone. Recently, we have reported the application of these ligands as useful catalysts for transfer hydrogenation of prochiral ketones (Chakka et al., 2009), Henry reactions, hydrogenation of olefins (Peters et al. 2010) and Diels-Alder reactions (Naicker et al., 2010a).

Compound 1 was derived from commercially available S-phenyl glycine and formaldehyde. The absolute stereochemistry was confirmed to be S at the C9 position from proton NMR spectroscopy. (Peters et al. 2010).

From the crystal structure it is evident that the N-containing six membered ring assumes a half chair conformation (Fig. 1), in which the 1—N1—C9—C8 bond has a torsion angle of 68.7 (3)°. This observation is similar to analogous structures that we have reported recently (Chakka et al., 2010) and (Naicker et al., 2010b).

The molecule exhibits intermolecular hydrogen bonding, which involves the atom O1 which links the molecules together see Table 1 and Fig. 2.

Experimental

(S)-2-methyl-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (1.5 g, 7.8 mmol) was dissolved in DMF (15 ml) followed by addition of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) hydrochloride (8.8 mmol), hydroxybenzotriazole (0.81 g, 8.3 mmol), a catalytic amount of 4-dimethylaminopyridine and benzyl amine (8.3 mmol). The reaction mixture was then stirred at room temperature until no more starting material could be detected by TLC analysis (approximately 1 h). The reaction mixture was poured into 30 volumes of chilled water; the mixture was then extracted twice with ethyl acetate. The extracts were combined, washed with 5% HCl (aq) to remove latent EDC urea, dried over anhydrous magnesium sulfate and then concentrated to dryness affording the crude product which was purified by column chromatography.

Melting point 91–95 ^oC. [α]²⁰_D -7.93 (c 0.21 in CHCl₃).

IR (neat) n_max: 3281, 2923, 1646, 1548, 1454, 1240, 739, 696 cm^-1.

¹H NMR (400 MHz, CDCl₃) δ = 2.78 (d, 3H), 3.12 (m, 2), 3.52 (t, 1H), 3.66 (m, 3H), 3.78 (d, 1H), 6.99 (d, 1H), 7.19 (m, 3H), 7.30 (m, 6H)

Recrystallization from EtOAc afforded colourless crystals suitable for X-ray analysis.